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Headache in Epilepsy: Prevalence and Clinical Features

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Headache in Epilepsy: Prevalence and Clinical Features Mainieri et al. The Journal of Headache and Pain (2015) 16:72 DOI 10.1186/s10194-015-0556-y RESEARCH ARTICLE Open Access Headache in epilepsy: prevalence and clinical features G Mainieri1,2, S Cevoli1, G Giannini1,2, L Zummo1,2,3, C Leta1,2, M Broli1,2, L Ferri1,2, M Santucci1,2, A Posar1,2, P Avoni1,2, P Cortelli1,2, P Tinuper1,2 and Francesca Bisulli1,2* Abstract Background: Headache and epilepsy are two relatively common neurological disorders and their relationship is still a matter of debate. Our aim was to estimate the prevalence and clinical features of inter-ictal (inter-IH) and peri-ictal headache (peri-IH) in patients with epilepsy. Methods: All patients aged ≥ 17 years referring to our tertiary Epilepsy Centre were consecutively recruited from March to May 2011 and from March to July 2012. They underwent a semi-structured interview including the International Classification Headache Disorders (ICHD-II) criteria to diagnose the lifetime occurrence of headache.χ2-test, t-test and Mann–Whitney test were used to compare clinical variables in patients with and without inter-IH and peri-IH. Results: Out of 388 enrolled patients 48.5 % had inter-IH: migraine in 26.3 %, tension-type headache (TTH) in 19.1 %, other primary headaches in 3.1 %. Peri-IH was observed in 23.7 %: pre-ictally in 6.7 %, ictally in 0.8 % and post-ictally in 19.1 %. Comparing patients with inter-ictal migraine (102), inter-ictal TTH (74) and without inter-IH (200), we found that pre-ictal headache (pre-IH) was significantly represented only in migraineurs (OR 3.54, 95 % CI 1.88-6.66, P < 0.001). Post-ictal headache (post-IH) was significantly associated with both migraineurs (OR 2.60, 95 % CI 1.85-3.64, P < 0.001) and TTH patients (OR 2.05, 95 % CI 1.41-2.98, P < 0.001). Moreover, post-IH was significantly associated with antiepileptic polytherapy (P < 0.001), high seizure frequency (P = 0.002) and tonic-clonic seizures (P = 0.043). Conclusions: Migraine was the most represented type of headache in patients with epilepsy. Migraineurs are more prone to develop pre-IH, while patients with any inter-IH (migraine or TTH) are predisposed to manifest a post-IH after seizures. Keywords: Headache; Epilepsy; Migraine; Pre-ictal headache; Post-ictal headache Background and therapeutic overlap [2]. Studies on the association be- Epilepsy and primary headache disorders affect individ- tween epilepsy and other types of primary headache are uals of all ages worldwide. Several studies have been difficult to perform as tension-type headache (TTH) is ex- performed to attest if there is a relationship between tremely common in the general population [3] whereas the two conditions, in order to verify the existence of a cluster headache is very rare [4]. For this reason most causal association or if the two disorders can occur in studies analyzing the prevalence of headache in patients the same individual by chance. In the last century with epilepsy focused only on migraine and results remain Gowers first advanced the clinical hypothesis of a relation- controversial (Table 1) [5–21]. ship between epilepsy and migraine [1] since the two con- According to its temporal relationship with epileptic sei- ditions show a well-recognized clinical, pathophysiological zures, headache can be classified as inter-ictal (inter-IH) or peri-ictal (peri-IH). Inter-IH is not temporally related * Correspondence: [email protected] to seizures, whereas peri-IH manifests in their time frame 1IRCCS Istituto delle Scienze Neurologiche di Bologna, AUSL di Bologna, (pre-ictally, ictally, post-ictally) [7, 8]. Literature data on Bologna, Italy 2Department of Biomedical and Neuromotor Sciences, University of Bologna, the relation between inter-IH (in particular migraine) and Bellaria Hospital, Via Altura, 3 – 40139, Bologna, Italy peri-IH are controversial owing to the methodological Full list of author information is available at the end of the article © 2015 Mainieri et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Mainieri et al. The Journal of Headache and Pain (2015) 16:72 Page 2 of 10 Table 1 Literature prevalence of migraine in patients with epilepsy Authors Sample M/F Age Methods Results N of pts yrs Migraine Schon and Blau 1987 [5] 100 39/61 32 mean Interview 9 % Ottman and Lipton 1994 [6] 1948 40 %/ ≥18 Structured telephone interviews + medical 24 % 60 % records review for 60 % of probands Ito and Shachter 1996 [7] 162 82/80 19-65 range Questionnaires mailed to the subjects + medical NAa records review Ito et al. 1999 [8] 109 36/73 38 ± 12 meanb Questionnaire + interview + medical records review 12.8 % Velioglu and Ozmenoglu 1999[9] 412 212/200 15-70 range Interview with a standardized questionnaire 14 % Leniger et al. 2001 [10] 341 154/187 40 ± 15 mean Interview with a standardized questionnaire 18.2 % Karaali Savrun et al. 135 80/55 ≥10 Questionnaire administered to patients 14.8 % 2002 [11] Förderreuther et al. 2002 [12] 110 69/41 35.2 mean Semi-standardized interview 10 %b Ito et al. 2004 [13] 364 163/201 12-81 range Structured interview with standardized questionnaire 8 % Syvertsen et al. 2007 [14] 109 44/65 20-71 range Questionnaire + semi-structured telephonic interview 20 % Kwan et al. 2008 [15] 227 98/129 36.0 ± 11.3 mean Interview with standardized questionnaire + seizures 6.6 %b and headache diary over the 3-month observation period + final interview HELP Study Group 2010 [16] 597 348/249 ≥13 Questionnaire at initial visit 12.4 % Tonini et al. 2012 [17] 492c 154/338 ≥18 Direct interview with questionnaire 18.3 %b Duchaczek et al. 2012 [18] 201 106/95 ≥18 Semi-structured interview 11 % Winawer et al. 2013 [19] 730d 285/445 ≥12 Telephone or in-person interview + medical 25.2 %e record abstraction Gameleira et al. 2013 [20] 304 141/163 4-88 range Patients evaluated at the epilepsy clinic 32.9 %f Wang et al. 2014 [21] 1109 607/502 ≥18 Self-administered questionnaire + standardized 12.53 % semi-structured telephone interview N, number; pts, patients; M, males; F, females; yrs, years; NA, not available aa prevalence of inter-ictal migraine is not clearly identifiable; the authors report a prevalence of inter-ictal headache in 64 % of patients, approximately a half of them with a pounding quality and almost 70 % of them often accompanied by nausea and/or vomiting, photophobia or phonophobia bcalculated by the authors cthis multicenter study involved 1167 patients from epilepsy and headache centers, we considered only patients with epilepsy d371 probands, 231 siblings, 128 parents: all with epilepsy; e23.5 % probands, 22.5 % siblings, 35.2 % parents fthe authors of the study does not distinguish between inter-ictal migraine and post-ictal headache with migrainous features heterogeneity of previous studies [5–21]. Moreover, in the Study design and participants context of seizure-related headaches, entities identified as This is a cross-sectional study conducted at the out- “migralepsy” or “epileptic headache” are still matter of dis- patient clinic of our tertiary Epilepsy Center between cussion [22]. March and May 2011 and March and July 2012. Patients The aim of this study was to estimate the prevalence aged ≥ 17 years were consecutively asked to participate of headache in adult patients with epilepsy, describing in the study and a self-report form was administered to its clinical features and temporal relationship with seiz- those who accepted. This form dichotomously ruled out ure occurrence. patients who reported a lifetime presence of headache and patients who had never suffered from headache. If patients confirmed the occurrence of headache, trained Methods physicians (GM, CL, LF), blinded to the patient’s diagno- The institutional review board of the IRCCS Institute of sis, conducted a semi-structured interview characterizing Neurological Sciences of Bologna approved the project. the type of inter-IH and peri-IH, if present. Headache Clinical investigations have been carried out in accord- data were revised by headache experts (SC, GG, PC), ance with the Helsinki Declaration adopted by the 18th who validated the diagnosis according to ICHD-II cri- World Medical Assembly in Helsinki, in 1964, as last teria [23]. Expert epileptologists (FB, PT, PA, MS) clas- amended by the World Medical Assembly. sified epileptic seizures and syndromes according to Mainieri et al. The Journal of Headache and Pain (2015) 16:72 Page 3 of 10 the 2010 International League Against Epilepsy (ILAE) generalized seizure and resolves within 72 h after the seiz- Commission report [24]. ure” [23]. We collected data on the lifelong presence of All patients with a diagnosis of epilepsy were in- headache and verified if headache attacks had occurred in cluded in the study. We excluded patients who had ar- the three months prior to the interview. We defined as rived for a first visit and proved not to be affected by “inter-ictal headache” all headaches that manifested within epilepsy (i.e. psychogenic non-epileptic seizures, sleep a time period of the epileptic disease and whose attacks disorders, syncope, dystonia), patients with a doubtful were not temporally related to an epileptic seizure. epilepsy diagnosis, patients who had only a single seiz- According to ICHD-II criteria [23], inter-IH was divided ure, and patients with a severe mental retardation.
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